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Bioengineering Seminar Series

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    The Artificial Pancreas
    (Georgia Institute of Technology, 2011-04-07) Klonoff, David
    An artificial pancreas is an engineered device for treating diabetes, which is one of the greatest epidemic diseases in the US and worldwide. In the US 105 million people have diabetes or prediabetes. An artificial pancreas is a device containing only synthetic materials which substitutes for an endocrine pancreas by sensing the BG level, determining the amount of insulin needed, and then delivering an appropriate amount of insulin. An artificial pancreas uses closed loop control by measuring glucose continuously and then continuously adjusting an infused dose of insulin. The three main components of an artificial pancreas are: 1) a continuous glucose sensor; 2) an insulin infusion pump; and 3) a controller using software to determine the insulin dose. Wireless radios link the components. Better sensors, better insulin delivery, and better control algorithms are all needed to create a viable system. Improvements in all three components are currently being developed. Control algorithms typically use either a Proportionate/Integral/Derivative method or a Model Predictive Control method. Each type of control formula has advantages and disadvantages. A controversy in control of a closed loop system involve how sensitively to program the controller to deliver a meal bolus of insulin in case of a rise in blood glucose, which could represent either a meal requiring insulin right away or a random fluctuation requiring no additional insulin. A second controversy involves how to protect a patient from hypoglycemia, because insulin lowers elevated glucose levels, but no part of a classical artificial pancreas system can raise depressed glucose levels. Glucagon is being tested as a rescue treatment for hypoglycemia in closed loop control systems. Current closed loop systems have already been demonstrated to be effective in specified closely monitored inpatient environments. Emerging and future closed loop glycemia maintenance systems will incorporate many inputs besides glucose levels. These inputs will be necessary to use much more complex models of glycemia which can be nuanced by such factors as day-to-day insulin sensitivity, meals, exercise, stress, and individual differences in the time course of insulin action. In the future, an artificial pancreas system will provide telemedicine care in case of hypoglycemic emergencies and will likely offer an option for a remote healthcare provider to assume control of the insulin programming to override sensor-determined control. Recent reports and meetings by FDA, Diabetes Technology Society, NIH, and Juvenile Diabetes Research Foundation are intended to overcome barriers to designing robust clinical trials of artificial pancreas systems. The first artificial pancreas product is approved in Europe and is at an early stage of undergoing testing in the United States. This product contains a low glucose suspend feature in the event of a hypoglycemic episode, which fails to result in acknowledgement of the glucose level or adjustment of the insulin dose. At this point in order to see a commercial closed loop product be approved for marketing and reimbursement, we will need to collect additional data about the safety, efficacy, and economic impact of these systems. A well designed artificial pancreas system will revolutionize diabetes care.
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    Enhancing Solute Transport in Immature Cartilage and Engineered Tissue Constructs
    (Georgia Institute of Technology, 2011-03-08) Ateshian, Gerard A.
    Osteoarthritis (OA) is a debilitating degenerative disease that afflicts an estimated 27 million Americans age 25 and older. This disease leads to the progressive degradation of the articular layers of diarthrodial joints, significantly compromising the main function of cartilage as a load bearing material, leading to pain and limiting activities of daily living. Cartilage functional tissue engineering is a highly promising technology that aims to provide a biological replacement to worn articular layers, as a modality that considerably expands the limited options in the treatment of this disease. Though cartilage degeneration is occasionally limited to small focal areas within articular layers, OA generally becomes symptomatic when degradation has spread over much greater surface areas (such as greater than 25 percent of the articular layer). Unfortunately, functional tissue engineering of large cartilage constructs is significantly constrained by the balance of nutrient transport and consumption. Several studies have shown that matrix deposition and elaboration of functional properties preferentially occurs near the periphery of constructs, where nutrient supply from the surrounding culture medium is most abundant, whereas cells in the interior receive less nutrients and produce less matrix, with poorer functional properties. In this presentation, we show that dynamic mechanical loading can enhance solute transport by up to an order of magnitude, and this enhancement can be considerably accelerated by placing channels in the constructs.
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    Functional molecular imaging in the brain
    (Georgia Institute of Technology, 2011-02-24) Jasanoff, Alan
    Functional magnetic resonance imaging (fMRI) with contrast agents sensitive to neural activity could have great impact in neuroscience by combining noninvasive whole-brain coverage with molecular-level specificity for neuronal events. My laboratory is developing molecular fMRI approaches based on molecular sensors we have designed to detect intra- and extracellular signalling events in the nervous system. Our sensors are built on a variety of chemical platforms, ranging from small molecules to nanoparticles. Protein-based contrast agents are of particular interest to us because of the possibility of gene-based brain delivery strategies and the availability of powerful protein engineering techniques. Here we describe molecular engineering of several MRI sensors for neural activity, as well as the first efforts in our laboratory to perform functional neuroimaging with molecular specificity in living brains.
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    Homogeneity tests among groups for microsatellite data
    (Georgia Institute of Technology, 2011-01-27) Pinheiro, Hildete Prisco
    We propose a homogeneity test among groups on a quadratic distance measure. The underlying mutation process in the microsatellite loci is studied using the stepwise mutation model. Asymptotic normality of the test statistic is proven under very mild regularity conditions. Resampling methods, such as jackknife, are used in the application to build confidence intervals for the difference in allelic variation between and within groups. The method is applied in a real data to test whether there are differences in the distribution of the repeated sequence among groups defined by ethnicity and alcoholism index (ALDX1).
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    Design Principles for Cytokine-Neutralizing Polymers
    (Georgia Institute of Technology, 2009-11-19) Washburn, Newell R.
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    Smart Biomaterials Inspired by Nature's Mechanisms
    (Georgia Institute of Technology, 2009-10-29) Murphy, William L.
    Control over the soluble signals that cells encounter in their local environment is a common theme in natural tissue formation, and also an emerging theme in functional tissue engineering strategies. This concept is particularly important in stem cell-based applications, in which local soluble signals can dictate cell fate decisions. Therefore, there is significant interest in using bioengineering approaches to control soluble signaling in the stem cell microenvironment. Nature often achieves intricate control over local soluble signaling via specific, non-covalent interactions. Inspired by these natural interactions, we are interested in creating biomaterials that actively regulate soluble signaling. For example, our recent studies have used engineered protein-peptide and protein-mineral interactions to build new classes of materials that are bio-responsive and capable of regulating growth factor signaling. This talk will specifically highlight bio-inspired protein conformational shifts and engineered growth factor sequestering as mechanisms to regulate stem cell behavior upon and within biomaterials.
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    EGFR Family Gymnastics
    (Georgia Institute of Technology, 2009-10-22) Griffith, Linda G.
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    Scalable Manufacture of Cells
    (Georgia Institute of Technology, 2009-09-10) Rao, Mahendra S.
    Preparing cells for therapy requires developing a scalable GMP'able model for cell culture for the undifferentiated cells and for the differentiated cells derived from them. It is also important to develop testing processes and process for freezing and thawing and selection. Using dopaminergic neuron differentiation as an example I will discuss developing a protocol for obtaining dopaminergic neurons suitable for therapy or for screening.
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    Tissue Engineering and Regenerative Medicine: A Surgeon’s Perspective
    (Georgia Institute of Technology, 2005-04-08) Vacanti, Joseph P.
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    Professional Opportunities in the Pharmaceutical Industry in the 21st Century
    (Georgia Institute of Technology, 2004-10-29) Wasserman, Martin A.